medchem 19 Flashcards
to inhibit an enzyme we introduce a drug to the —- to bind — and —- and they usually react with —- and form —-
amino acids such as serine contains —-
- active site to bind irreversibly with it and blocks it permemntatlu
- amino acids and forms covelent bonds
- reactive 0h commonly present in enexzyme reactive site
the mode of action of aspirin isinhibiting —– and it reacts with —–
- inhibits PGH2 or COX aka cycloocygenase
- serine residue in the active site which has OH
ester ( aspirin ) + alcohol ( serine ) –> inhibited enzyme + phenol ( salicylic acid )
inhibited enzyme + phenol ( salicylic acid )
mode of action of the penicillin
inhibits glycopeptiode transpeptidase and it reacts with serine residue in the active site of the enzyme
lactam - cylic amid (penicillin ) + serine (oh) —>
inhibited enzyeme aka ester + amine
aspirin inhibits the enzyme called — this enzyme converts —-
( that’s how aspirin is an anti-inflammatory, anti - pyretic and analgesic agents )
prostaglandin -h2- sythesase or cylcoxyogenase ( COX)
converts archodonic acid into prostaglandin and thromoboxanes
prostaglandin is a hormone reposinble for
fever,pain, and inflammatory responses and has low concentrations so aspirin will relieve these symptoms
the side effects of the aspirin:
irritation for the gastric mucosa and the nephrotoxixty aka the alteration of salt and water in the kidney
prostaglandins are made up of —- with the enzyme —- being the catalyst
arachidonic acid , pgh2
aspirin is an example of
NSAIDS : non steroid anti inflammatory drug which inhibits he cox
the interaction of arachondic acid with cox
arachidonic acid ( sign is -ve )will enter the cox active site and will bind to agginine ( which is +ve) 119 to form salt bridges through the carboxylate group which will then be converted to prostogaldin
how does aspirin inhibits cox ?
acetyl grou ( ch3c0 ) of aspirin will be transferred to alcohol group of the enzyme in the nucleophilic susbution reaction leaving the enzyme inhibited
aspirin inhibition summary
( CHECK THE MECHANISM AND CHECK SLIDE 13)
- the aspirin inhibits cox by binding to arginine 119 ( in the electrostatic interactions )
- transfers the acetyl group to serine residue near the entrance of the active site
- the acetylation is irreversible and prevents the entry of arachodnic acid by the steric effects
the two types of cox
- COX-1 : housekeeping enzyme reposible for the protection of gastric, vacuslar , Renal and inhibition of the COX 1 leads to their toxicity and the adverse side effect is their damage to the kidney and gastric mucosa
- C0X 2: responds to the stimuli and inhibition of it leads to anti-inflammatory, analgestic and anti pyretic effects and its reposnisbel for mediate inflammation pain and fever. it’s the therapeutic effects of aspirin . Selective COX 2 inhibitor should have the therapeutic effects but not the side effects of aspirin
the difference between cox 1 and cox 2
- the difference is the cox active site in position 523
- cox 1 is isoleucine IIe 523 , slightly bigger
- cox 2 is valine 523 , and has one less ch2 so it has slightly bigger binding pocket
celecoxib is selective inhibitor for —
- cox 2
- the celecoxib fits into the active site region of cox 2 as the sulfoamide group fits into the side pocket and prevents the entry of arachondic acid.
- it causes less ulceration in the stomach and intestine than other NSAIDS
-doesnt work w/ COX 1 because sulfoamide can’t be accomdated due to the sterically bulkier isoleucine amino acid so arachnid acid can enter unimpeded .
penicillin stucture:
penicillin properties:
- contains cyclic amid lactam and its b lactam because it has two additional carbons in the amide/lactam ring.
- it also has sulphur in the five membered ring
- b- lactam ring is strained making it reactive and liable bond between the carbonyl group and nitrogen
- bicyclic system has a well defined shape and a half open book shape, it mimic the topology of the enzyme bc of its well defined shape
- its not a planer so it makes it more stable and resonances is reduced
penicillin leads to inactive —- which inhibits the —-
- glycopeptide transpeptidase
- cell wall biosynthesis
the reason why lactam ( amide ) + alcohol –> amine + ester can occur:
- the structure of penicillin has lactam with different structure from amides
- resonance is reduced and the carbonyl in the b lactam becomes more like keton and less like amide
- and the reactivity of the b lactam towards nucleophiles is more than amides
- its not a planer structure ( 2 fused rings lie at an angle )because of the excessive ring strain ( the bond angles are smaller than 109 )
the last step of the action of reaction mechanism of penicillin with GPTase is
release of the ring strain
( CHECK THE MEHCANISM )
